This application for a Research Scientist Award is based on six research projects (five are funded and the sixth will be funded). The overall objective is to investigate two aspects of drug abuse: (1) the determinants of drug reinforced behavior, and (2) the effects of reinforcing drugs on other behaviors (e.g., impaired performance, tolerance, aggression). These studies span three areas: animal laboratory, human laboratory, and outpatient clinic. A unifying theme of the studies is an analysis of drug effects in terms of their behavioral pharmacology. A related theme is to interrelate the findings and problems of the three areas. The first project concerns acquisition of drug reinforcing effects. The objective is to study the development of reinforcing effects over time by using several strategies including repeated probes with the new drug. The study will be conducted with rhesus monkeys, and the drugs (cocaine, pentobarbital, etonitazene) will be taken orally. The second project examines behavior of rhesus monkeys reinforced by oral delivery of cocaine. A broad range of variables will be studied to determine their effects on oral cocaine reinforced behavior. The third project studies the effects of the joint actions of behavioral and pharmacological interventions designed to reduce cocaine and heroin abuse in outpatients. The fourth project investigates marijuana and cocaine effects on escape and aggressive behavior studied under controlled laboratory conditions with human subjects. The fifth project deals with the effects of sedative and hypnotic drugs on human performance. The sixth projects concerns the analysis of behavioral tolerance to ethanol in human subjects.